Skip to main content
SpringerLink
Log in

Analysis of the P53N a Novel Protein Encoded on Chromosome 22q12.1-12.3 in Glioblastomas and Ependymomas Specimens

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

The P53N gene maps precisely to human chromosome sub-band 22q12.1-12.3, a region where loss of heterozygosity has been reported in 30% of astrocytic tumors and associated with progression to anaplasia. Moreover, a putative tumor suppressor gene has been indicated on 22q11 region involved in pathogenesis of ependymal tumors. Our objectives to examine the expression level of novel membrane-associated protein (termed P53N) encoded by a novel human gene on chromosome 22q12.1-12.3 in glioblastomas and ependymomas. Serial analysis of gene expression (SAGE) and immunofluorescence analysis of the P53N in the brain tumor tissues were performed. Our analysis revealed that there was high expression of the P53N mRNA in brain ependymoma and brain well-differentiated astrocytoma libraries. The P53N protein. P53N protein contains a high mobility group (HMG) domain at amino acid positions 301 to 360 expressed highly in glioblastoma and ependymoma specimens. Anti-P53N carboxyl-terminal peptide antibody localized the P53N protein to the cytoplasmic membranes of protoplasmic astrocytes in the glioblastoma and ependymoma specimens. These results are in good agreement with the SAGE analysis and the predicted transmembrane topology for the P53N protein and support a possible transmembrane model in which the P53N contains a predicted transmembrane region with its amino terminus localized to the inside of the cytoplasmic membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Burger PC, Vogel FS, Green SB (1985) Glioblastoma multiforme and anaplastic astrocytoma Pathologic criteria and prognostic implications. Cancer 56:1106–1111

    Article  CAS  Google Scholar 

  • Ekstrand AJ, Sugawa N, James CD et al (1992) Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. Proc Natl Acad Sci USA 89(10):4309–4313

    Article  CAS  Google Scholar 

  • Euskirchen P, Radke J, Schmidt MS et al (2017) Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma. PLoS One 12(9):e0185376

    Article  Google Scholar 

  • Goodwin GH, Sanders C, Johns EW (1973) A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem 38:14–19

    Article  CAS  Google Scholar 

  • Grosschedl R, Giese K, Pagel J (1994) HMG domain proteins: architectural elements in the assembly of nucleoprotein structures. Trends Genet 10(3):94–100

    Article  CAS  Google Scholar 

  • Hartmann C, Nümann A, Mueller W et al (2004) Fine mapping of chromosome 22q tumor suppressor gene candidate regions in astrocytoma. Int J Cancer 108(6):839–844

    Article  CAS  Google Scholar 

  • Hulbanni S, Goodman PA (1976) Glioblastoma multiforme with extraneural metastases in the absence of previous surgery. Cancer 37:1577–1583

    Article  CAS  Google Scholar 

  • Ikeda M, Arai M, Okuno T et al (2003) TMPDB: a database of experimentally-characterized transmembrane topologies. Nucleic Acids Res 31(1):406–409

    Article  CAS  Google Scholar 

  • Ino Y, Silver JS, Blazejewski L et al (1999) Common regions of deletion on chromosome 22q12.3-q13.1 and 22q13.2 in human astrocytomas appear related to malignancy grade. J Neuropathol Exp Neurol 58(8):881–885

    Article  CAS  Google Scholar 

  • Jantzen HM, Admon A, Bell SP et al (1990) Nucleolar transcription factor hUB contains a DNA-binding motif with homology to HMG proteins. Nature 344(6269):830–836

    Article  CAS  Google Scholar 

  • Jemal A, Thomas A, Murray T et al (2002) Cancer Statistics. CA. Cancer J Clin 52:23–47

    Article  Google Scholar 

  • Jennings MT, Iyengar S (2001) The molecular genetics of therapeutic resistance in malignant astrocytomas. Am J Pharmacogenomics 1(2):93–99

    Article  CAS  Google Scholar 

  • Kleihues P, Burger PC, Cavenee WK (1997) Glioblastoma. WHO Classification: pathology and genetics of tumors of the nervous system, 1st edn. Lyon, France, International Agency for Research on Cancers, pp 16–24

    Google Scholar 

  • Kraus JA, de Millas W, Sörensen N et al (2001) Indications for a tumor suppressor gene at 22q11 involved in the pathogenesis of ependymal tumors and distinct from hSNF5/INI1. Acta Neuropathol 102(1):69–74

    Article  CAS  Google Scholar 

  • Lang FF, Miller DC, Koslow M et al (1994) Pathways leading to glioblastoma multiforme: a molecular analysis of genetic alterations in 65 astrocytic tumors. J Neurosurg 81(3):427–436

    Article  CAS  Google Scholar 

  • Libermann TA, Nusbaum HR, Razon N et al (1985) Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin. Nature 313(5998):144–147

    Article  CAS  Google Scholar 

  • Louis DN, Holland EC, Cairncross JG (2001) Glioma classification: a molecular reappraisal. Am J Pathol 159(3):779–786

    Article  CAS  Google Scholar 

  • Louis DN, von Deimling A, Chung RY et al (1993) Comparative study of p53 gene and protein alterations in human astrocytic tumors. J Neuropathol Exp Neurol 52(1):31–38

    Article  CAS  Google Scholar 

  • Nakamura M, Yang F, Fujisawa H et al (2000) Loss of heterozygosity on chromosome 19 in secondary glioblastomas. J Neuropathol Exp Neurol 59(6):539–543

    Article  CAS  Google Scholar 

  • Nauen D, Haley L, Lin MT et al (2016) Molecular analysis of pediatric oligodendrogliomas highlights genetic differences with adult counterparts and other pediatric gliomas. Brain Pathol 26:206–214

    Article  CAS  Google Scholar 

  • Newcomb EW, Cohen H, Lee SR et al (1998) Survival of patients with glioblastoma multiforme is not influenced by altered expression of p16, p53, EGFR, MDM2 or Bcl-2 genes. Brain Pathol 8(4):655–667

    Article  CAS  Google Scholar 

  • Newcomb EW, Madonia WJ, Pisharody S et al (1993) A correlative study of p53 protein alteration and p53 gene mutation in glioblastoma multiforme. Brain Pathol 3(3):229–235

    Article  CAS  Google Scholar 

  • Nigro JM, Baker SJ, Preisinger AC et al (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342(6250):705–708

    Article  CAS  Google Scholar 

  • Riemenschneider MJ (2009) Reifenberger G. Molecular neuropathology of gliomas. Int J Mol Sci 10:184–212

    Article  CAS  Google Scholar 

  • Smith JS, Tachibana I, Lee HK et al (2000) Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using fluorescence in situ hybridization and novel microsatellite markers. Genes Chromosomes Cancer 29(1):16–25

    Article  CAS  Google Scholar 

  • Surawicz TS, Davis F, Freels S et al (1998) Brain tumor survival: results from the National Cancer Data Base. J Neurooncol 40:151–160

    Article  CAS  Google Scholar 

  • Ueki K, Ono Y, Henson JW, Efird JT et al (1996) CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56(1):150–153

    CAS  PubMed  Google Scholar 

  • von Deimling A, Eibl RH, Ohgaki H et al (1992) p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52(10):2987–2990

    Google Scholar 

  • von Deimling A, Louis DN, von Ammon K et al (1992) Association of epidermal growth factor receptor gene amplification with loss of chromosome 10 in human glioblastoma multiforme. J Neurosurg 77(2):295–301

    Article  Google Scholar 

  • Wang C, McCarty IM, Balazs L et al (2002) A prostate-derived cDNA that is mapped to human chromosome 19 encodes a novel protein. Biochem Biophys Res Commun 296:281–287

    Article  CAS  Google Scholar 

  • Watanabe K, Sato K, Biernat W et al (1997) Incidence and timing of p53 mutations during astrocytoma progression in patients with multiple biopsies. Clin Cancer Res 3(4):523–530

    CAS  PubMed  Google Scholar 

  • Watanabe K, Tachibana O, Sata K et al (1996) Overexpression of the EGF receptor and p53 mutations are mutually exclusive in the evolution of primary and secondary glioblastomas. Brain Pathol 6(3):217–223

    Article  CAS  Google Scholar 

  • Wong AJ, Ruppert JM, Bigner SH et al (1992) Structural alterations of the epidermal growth factor receptor gene in human gliomas. Proc Natl Acad Sci USA 89(7):2965–2969

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Chiang Wang, Ph.D., for assisting Dr. Bruce M. Frankel. We also thank Sigma Genosys for the generation of the anti-P53N carboxyl-terminal peptide antibody.

Funding

This study was partially supported in part by the NIH sponsored grants to Bruce M. Frankel (1R01FD003542-01), Departments of Neurosurgery and Urology at the University of Tennessee Health Science Center, the Assisi Foundation of Memphis, and a grant from the American Brain Tumor Association (to BMF).

Author information

Authors and Affiliations

  1. Department of Neurosurgery (Divisions of Neuro-Oncology), MUSC Brain & Spine Tumor Program CSB 310, Medical University of South Carolina, Charleston, SC, 29425, USA

    Bruce M. Frankel, David Cachia, Sunil J. Patel & Arabinda Das

Authors
  1. Bruce M. Frankel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Cachia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sunil J. Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arabinda Das
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceived and designed the experiments: BMF. Analyzed the data: BMF. Wrote the draft of the manuscript: BMF, AD, and DC. Contributed to the writing of the manuscript: BMF, AD, SJP, and DC (all authors). Agree with manuscript results and conclusions: all authors. Jointly developed the structure and arguments for the paper: all authors. Made critical revisions and approved final version: BMF. All authors reviewed and approved of the final manuscript.

Corresponding author

Correspondence to Arabinda Das.

Ethics declarations

Ethics Approval and Consent to Participate

All participants signed informed consent. Subjects gave their written, informed consent to participate.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frankel, B.M., Cachia, D., Patel, S.J. et al. Analysis of the P53N a Novel Protein Encoded on Chromosome 22q12.1-12.3 in Glioblastomas and Ependymomas Specimens. J Mol Neurosci 71, 1714–1722 (2021). https://doi.org/10.1007/s12031-021-01808-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-021-01808-8

Keywords

Search

Navigation